ArticleMolecular biology of the cell2009
Sequence-specific retention and regulated integration of a nascent membrane protein by the endoplasmic reticulum Sec61 translocon.
Article in Molecular biology of the cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
- Membrane Protein Insertion in Cells: Principles, Pathways, and Quality Control.Chemical reviews · 2026Review
- Functional Consequences of CFTR Interactions in Cystic Fibrosis.International journal of molecular sciences · 2024Review
- Transmembrane Helices 7 and 8 Confer Aggregation Sensitivity to the Cystic Fibrosis Transmembrane Conductance Regulator.International journal of molecular sciences · 2023Article
- CFTR Folding: From Structure and Proteostasis to Cystic Fibrosis Personalized Medicine.ACS chemical biology · 2023Review
- Methods to study folding of alpha-helical membrane proteins in lipids.Open biology · 2022Review
- CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput screening system.Molecular systems biology · 2022Article
- Small Hsps as Therapeutic Targets of Cystic Fibrosis Transmembrane Conductance Regulator Protein.International journal of molecular sciences · 2021Review
- The Dynamic SecYEG Translocon.Frontiers in molecular biosciences · 2021Review
- Cell-free expression tools to study co-translational folding of alpha helical membrane transporters.Scientific reports · 2020Article
- Regulation of CFTR Biogenesis by the Proteostatic Network and Pharmacological Modulators.International journal of molecular sciences · 2020Review
- Understanding GPCR Recognition and Folding from NMR Studies of Fragments.RSC advances · 2018Article
- Refined topology model of the STT3/Stt3 protein subunit of the oligosaccharyltransferase complex.The Journal of biological chemistry · 2017Article
- Mycolactone reveals the substrate-driven complexity of Sec61-dependent transmembrane protein biogenesis.Journal of cell science · 2017Article
- From the endoplasmic reticulum to the plasma membrane: mechanisms of CFTR folding and trafficking.Cellular and molecular life sciences : CMLS · 2017Review
- NMR Investigation of Structures of G-protein Coupled Receptor Folding Intermediates.The Journal of biological chemistry · 2016Article
- Targeting Viral Proteostasis Limits Influenza Virus, HIV, and Dengue Virus Infection.Immunity · 2016Article
- The Ribosome-Sec61 Translocon Complex Forms a Cytosolically Restricted Environment for Early Polytopic Membrane Protein Folding.The Journal of biological chemistry · 2015Article
- Marginally hydrophobic transmembrane α-helices shaping membrane protein folding.Protein science : a publication of the Protein Society · 2015Review
- Mechanisms of integral membrane protein insertion and folding.Journal of molecular biology · 2015Review
- Structural and functional profiling of the lateral gate of the Sec61 translocon.The Journal of biological chemistry · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
A defining feature of eukaryotic polytopic protein biogenesis involves integration, folding, and packing of hydrophobic transmembrane (TM) segments into the apolar environment of the lipid bilayer. In the endoplasmic reticulum, this process is facilitated by the Sec61 translocon. Here, we use a photocross-linking approach to examine integration intermediates derived from the ATP-binding cassette transporter cystic fibrosis transmembrane conductance regulator (CFTR) and show that the timing of translocon-mediated integration can be regulated at specific stages of synthesis. During CFTR biogenesis, the eighth TM segment exits the ribosome and enters the translocon in proximity to Sec61alpha. This interaction is initially weak, and TM8 spontaneously dissociates from the translocon when the nascent chain is released from the ribosome. Polypeptide extension by only a few residues, however, results in stable TM8-Sec61alpha photocross-links that persist after peptidyl-tRNA bond cleavage. Retention of these untethered polypeptides within the translocon requires ribosome binding and is mediated by an acidic residue, Asp924, near the center of the putative TM8 helix. Remarkably, at this stage of synthesis, nascent chain release from the translocon is also strongly inhibited by ATP depletion. These findings contrast with passive partitioning models and indicate that Sec61alpha can retain TMs and actively inhibit membrane integration in a sequence-specific and ATP-dependent manner.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.